Signal enhancement ratio of multi-phase contrast-enhanced MRI: an imaging biomarker for survival in pancreatic adenocarcinoma.

OBJECTIVES: To evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the reference standard. METHODS: This retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015-2021). SER is defined as (SIlt - SIpre)/(SIea - SIpre), where SIpre, SIea, and SIlt represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan-Meier curves. RESULTS: The internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29-0.74, all p < 0.001) and epithelium (r = -0.23 to -0.71, all p < 0.001) across a wide post-injection time window (range, 25-300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17-2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25-2.41), p = 0.001). CONCLUSION: SER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC. CLINICAL RELEVANCE STATEMENT: The signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC. KEY POINTS: Imaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma. Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers. Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC.

Sex differences in the extent of acute axonal pathologies after experimental concussion.

Although human females appear be at a higher risk of concussion and suffer worse outcomes than males, underlying mechanisms remain unclear. With increasing recognition that damage to white matter axons is a key pathologic substrate of concussion, we used a clinically relevant swine model of concussion to explore potential sex differences in the extent of axonal pathologies. At 24 h post-injury, female swine displayed a greater number of swollen axonal profiles and more widespread loss of axonal sodium channels than males. Axon degeneration for both sexes appeared to be related to individual axon architecture, reflected by a selective loss of small caliber axons after concussion. However, female brains had a higher percentage of small caliber axons, leading to more extensive axon loss after injury compared to males. Accordingly, sexual dimorphism in axonal size is associated with more extensive axonal pathology in females after concussion, which may contribute to worse outcomes.

Correlations between the modification patterns mediated by pyroptosis-related genes, tumor microenvironment, and immunotherapy in soft tissue sarcoma.

Soft tissue sarcoma (STS) incidence, progression, and metastasis are tightly linked to the tumor microenvironment (TME). The modification patterns mediated by pyroptosis-related genes (PRGs) in STS are unknown regarding the immune cell infiltration landscape of TME, immunotherapy effect, and prognostic value. First, we downloaded STS samples from the Cancer Genome Atlas (TCGA) and gene-expression omnibus (GEO) databases. Based on 52 PRGs, 2 pyroptosis modification patterns were analyzed, and the associations of pyroptosis modification patterns with immune cell infiltration in the TME were elucidated systematically. To quantify PRG modification patterns in STS patients, we generated a pyroptosis scoring system using principal component analysis (PCA). We identified 2 distinct pyroptosis modification patterns in STS. Compared to PRG cluster A, the prognosis of cluster B was better. These 2 pyroptosis modification patterns corresponded to different characteristics of immune cell infiltration in the TME and biological behaviors. In the pyroptosis scoring system, a high pyroptosis score was connected to higher immune cell infiltration, stronger immune surveillance, immune-killing effects on tumor cells, and better clinical benefits. The results from 3 anti-PD1/PD-L1-treated immune cohorts demonstrated that higher pyroptosis scores are also closely connected to better immunotherapy results. We demonstrated that pyroptosis modification is essential to the STS microenvironment. Moreover, the pyroptosis score is a reliable and independent prognostic factor in STS patients, enabling a richer understanding of the STS microenvironment and the screening of immunotherapy candidates, predicting the immunotherapeutic effects for individual STS patients, and guiding the use of chemotherapy drugs.

Levels of trace metals and their impact on oocyte: A review.

Trace metals play a vital role in a variety of biological processes, but excessive amounts can be toxic and are receiving increasing attention. Trace metals in the environment are released from natural sources, such as rock weathering, volcanic eruptions, and other human activities, such as industrial emissions, mineral extraction, and vehicle exhaust. Lifestyle, dietary habits and environmental quality are the main sources of human exposure to trace metals, which play an important role in inducing human reproductive infertility. The purpose of this review is to summarize the distribution of various trace metals in oocyte and to identify the trace metals that may cause oocyte used in the design and execution of toxicological studies.

Pre-soil fumigation with ammonium bicarbonate and lime modulates the rhizosphere microbiome to mitigate clubroot disease in Chinese cabbage.

Background: Plasmodiophora brassicae is an ever-increasing threat to cruciferous crop production worldwide. Aims and methods: This study investigated the impact of pre-soil fumigation with ammonium bicarbonate (N) and lime (NB) to manage clubroot disease in Chinese cabbage through 16S rRNA gene amplification sequencing. Results: We found that soil fumigation with N and NB suppressed disease incidence by reducing the soil acidity and population of P. brassicae in the rhizosphere. Minimum disease incidence and maximum relative control effect of about 74.68 and 66.28% were achieved in greenhouse and field experiments, respectively, under the combined application of ammonium bicarbonate and lime (LNB) as compared with N, NB, and control (GZ). Microbial diversity analysis through Miseq sequencing proved that pre-soil fumigation with N, NB, and LNB clearly manipulated rhizosphere microbial community composition and changed the diversity and structure of rhizosphere microbes compared with GZ. Bacterial phyla such as Proteobacteria, Bacteriodetes, and Acidobacteria and fungal phyla including Olpidiomycota and Ascomycota were most dominant in the rhizosphere of Chinese cabbage plants. Soil fumigation with N and NB significantly reduced the abundance of clubroot pathogen at genus (Plasmodiophora) level compared with GZ, while decreased further under combined application LNB. Microbial co-occurrence network analysis showed a highly connected and complex network and less competition for resources among microbes under combined application LNB. Conclusion: We conclude that for environmentally friendly and sustainable agriculture, soil fumigation with combined ammonium bicarbonate and lime plays a crucial role in mitigating Chinese cabbage clubroot disease by alleviating soil pH, reducing pathogen population, and manipulating the rhizosphere microbiome.

Evaluation of drug interactions of Saposhnikoviae Radix and its major components with astragaloside IV and paeoniflorin using in vitro and in vivo experiments.

Saposhnikoviae Radix (SR) may enhance the pharmacodynamics of Huangqi Chifeng Tang (HQCFT) in the treatment of cerebral infarction according to our previous research, but the underlying mechanism is unknown. Herein, an in vivo pharmacokinetic assay in rats and in vitro MDCK-MDR1 cell assays were used to investigate the possible mechanism of SR, its main components, and its interactions with Astragali Radix (AR) and Paeoniae Radix (PR). An ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS)-based analytical method for quantifying astragaloside IV (ASIV) and paeoniflorin (PAE) in microdialysis and transport samples was developed. The pharmacokinetic parameters of SR were determined using noncompartmental analyses CCK-8 assays were used to detect the cytotoxicity of ASIV, PAE, cimifugin (CIM), prim-o-glucosylcimifugin (POG) and their combinations. Moreover, drug transport was studied using MDCK-MDR1 cells. Western blotting was performed to measure the protein expression levels of P-GP and MRP1. Claudin-5, ZO-1, and F-actin expression was determined via immunohistochemical staining of MDCK-MDR1 cells. harmacokinetic studies revealed that, compared with those of Huangqi Chifeng Tang-Saposhnikoviae Radix (HQCFT-SR), the Tmax of ASIV increased by 11.11 %, and the MRT0-t and Tmax of PAE increased by 11.19 % and 20 %, respectively, in the HQCFT group. Transport studies revealed that when ASIV was coincubated with 28 µM CIM or POG, the apparent permeability coefficient (Papp) increased by 71.52 % and 50.33 %, respectively. Coincubation of PAE with 120 µM CIM or POG increased the Papp by 87.62 % and 60.95 %, respectively. Moreover, CIM and POG significantly downregulated P-gp and MRP1 (P < 0.05), inhibited the expression of Claudin-5, ZO-1, and F-actin (P < 0.05), and affected intercellular tight junctions (TJs). In conclusion, our study successfully established a selective, sensitive and reproducible UPLC‒MS/MS analytical method to detect drug‒drug interactions between SR, AR and PR in vivo and in vitro, which is beneficial for enhancing the therapeutic efficacies of AR and PR. Moreover, this study provides a theoretical basis for further research on the use of SR as a drug carrier.

Advances on Senescence-associated secretory phenotype regulated by circular RNAs in tumors.

The components that comprise the senescence-associated secretory phenotype (SASP) include growth factors, proteases, chemokines, cytokines, and bioactive lipids. It drives secondary aging and disrupts tissue homeostasis, ultimately leading to tissue repair and regeneration loss. It has a two-way regulatory effect on tumor cells, resisting cancer occurrence and promoting its progression. A category of single-stranded circular non-coding RNA molecules known as circular RNAs (circRNAs) carries out a series of cellular activities, including sequestering miRNAs and modulating gene editing and expression. Research has demonstrated that a large number of circRNAs exhibit aberrant expression in pathological settings, and play a part in the onset and progress of cancer via modulating SASP factors. However, the research related to SASP and circRNAs in tumors is still in its infancy at this stage. This review centers on the bidirectional modulation of SASP and the role of circRNAs in regulating SASP factors across different types of tumors. The aim is to present novel perspectives for the diagnosis and therapeutic management of malignancies.

A novel g-C3N4-SH@konjac glucomannan composite aerogel for patulin removal from apple juice and its photocatalytic regeneration.

Patulin (PAT) is a hazardous mycotoxin frequently occurs in fruit industry. A reusable g-C3N4-SH@KG composite aerogel for PAT removal in a novel "dark adsorption-light regeneration" mode was prepared by thiol(-SH) functionalization and konjac glucomannan (KG) immobilization. The g-C3N4-SH@KG was characterized by SEM, FT-IR, XPS and UV-Vis DRS, and its PAT adsorption and photocatalytic regeneration behaviors and mechanisms were investigated. The g-C3N4-SH@KG exhibited good regeneration performance, maintaining 83% of PAT initial adsorption capacity (0.92 mg/g) after 5 "adsorption-regeneration" cycles. The adsorption process was endothermic and spontaneous. •OH and h+ generated by photocatalysis were the main substances that degraded PAT into two products and regenerated -SH. The g-C3N4-SH@KG could effectively remove PAT without negative impact on juice quality. The study provided a new strategy for the regeneration of thiol-functionalized PAT adsorbents, and a new idea for the application of non-selective photocatalysis in the control of food contaminations.

Deletion of Luzp2 Does Not Cause Hearing Loss in Mice.

Deafness is the prevailing sensory impairment among humans, impacting every aspect of one's existence. Half of congenital deafness cases are attributed to genetic factors. Studies have shown that Luzp2 is expressed in hair cells (HCs) and supporting cells of the inner ear, but its specific role in hearing remains unclear. To determine the importance of Luzp2 in auditory function, we generated mice deficient in Luzp2. Our results revealed that Luzp2 has predominant expression within the HCs and pillar cells. However, the loss of Luzp2 did not result in any changes in auditory threshold. HCs or synapse number and HC stereocilia morphology in Luzp2 knockout mice did not show any notable distinctions. This was the first study of the role of Luzp2 in hearing in mice, and our results provide important guidance for the screening of deafness genes.

A comprehensive review of biodetoxification of trichothecenes: Mechanisms, limitations and novel strategies.

Trichothecenes are Fusarium mycotoxins with sesquiterpenoid structure, which are widely occurred in grains. Due to high efficiency and environmental friendliness, biological detoxification methods have been of great interest to treat this global food and feed safety concern. This review summarized the biological detoxification methods of trichothecenes from three aspects, biosorption, biotransformation and biotherapy. The detoxification efficiency, characteristics, mechanisms and limitations of different strategies were discussed in detail. Computer-aided design will bring a new research paradigm for more efficient discovery of biodetoxifier. Integrating different detoxification approaches assisted with computational tools will become a promising research direction in the future, which will help to maximize the detoxification effect, or provide precise detoxification programs for the coexistence of various toxins at different levels in actual production. In addition, technical and regulatory issues in practical application were also discussed. These findings contribute to the exploration of efficient, applicable and sustainable methods for trichothecenes detoxification, ensuring the safety of food and feed to reduce the deleterious effects of trichothecenes on humans and animals.

In Situ Polymerization Facilitating Practical High-Safety Quasi-Solid-State Batteries.

Quasi-solid-state batteries (QSSBs) are gaining widespread attention as a promising solution to improve battery safety performance. However, the safety improvement and the underlying mechanisms of QSSBs remain elusive. Herein, a novel strategy combining high-safety ethylene carbonate-free liquid electrolyte and in situ polymerization technique is proposed to prepare practical QSSBs. The Ah-level QSSBs with LiNi0.83Co0.11Mn0.06O2 cathode and graphite-silicon anode demonstrate significantly improved safety features without sacrificing electrochemical performance. As evidenced by accelerating rate calorimetry tests, the QSSBs exhibit increased self-heating temperature and onset temperature (T2), and decreased temperature rise rate during thermal runaway (TR). The T2 has a maximum increase of 48.4 °C compared to the conventional liquid batteries. Moreover, the QSSBs do not undergo TR until 180 °C (even 200 °C) during the hot-box tests, presenting significant improvement compared to the liquid batteries that run into TR at 130 °C. Systematic investigations show that the in situ formed polymer skeleton effectively mitigates the exothermic reactions between lithium salts and lithiated anode, retards the oxygen release from cathode, and inhibits crosstalk reactions between cathode and anode at elevated temperatures. The findings offer an innovative solution for practical high-safety QSSBs and open up a new sight for building safer high-energy-density batteries.

The Role of Immune Cells in DKD: Mechanisms and Targeted Therapies.

Diabetic kidney disease (DKD), is a common microvascular complication and a major cause of death in patients with diabetes. Disorders of immune cells and immune cytokines can accelerate DKD development of in a number of ways. As the kidney is composed of complex and highly differentiated cells, the interactions among different cell types and immune cells play important regulatory roles in disease development. Here, we summarize the latest research into the molecular mechanisms underlying the interactions among various immune and renal cells in DKD. In addition, we discuss the most recent studies related to single cell technology and bioinformatics analysis in the field of DKD. The aims of our review were to explore immune cells as potential therapeutic targets in DKD and provide some guidance for future clinical treatments.

Three new species of Favolaschia (Mycenaceae, Agaricales) from South China.

The genus Favolaschia within the family Mycenaceae is characterised by the gelatinous basidiomata with poroid hymenophore and most species inhabit monocotyledonous plants. In this study, many samples covering a wide geographic range in China were examined morphologically and phylogenetically using concatenated ITS1-5.8S-ITS2-nLSU sequence data. Three new species clustering in Favolaschiasect.Anechinus, namely Favolaschiaimbricata, F.miscanthi and F.sinarundinariae, are described. Favolaschiaimbricata is characterised by imbricate basidiomata with pale grey to greyish colour when fresh and broadly ellipsoid basidiospores measuring 7-9 × 5-6.8 µm; F.miscanthi is characterised by satin white basidiomata when fresh, broadly ellipsoid basidiospores measuring 7.5-10 × 5.5-7 µm and inhabit rotten Miscanthus; F.sinarundinariae is characterised by greyish-white basidiomata when fresh, dark grey near the base upon drying, broadly ellipsoid to subglobose basidiospores measuring 7-9 × 5-7 µm and inhabit dead Sinarundinaria. The differences amongst the new species and their morphologically similar and phylogenetically related species are discussed. In addition, an updated key to 19 species of Favolaschia found in China is provided.

Impact of frailty on adverse outcomes in patients with abdominal aortic aneurysm undergoing surgery: a systematic review and meta-analysis.

OBJECTIVE: To explore the prognostic role of frailty in patients with abdominal aortic aneurysm (AAA) by conducting this systematic review and meta-analysis METHODS: We conducted an extensive literature search on PubMed, Web of Sciences, and Embase databases to identify studies that reported the association of frailty with postoperative complications, reintervention, or all-cause mortality in patients with AAA after surgery. Short-term mortality was defined by a combination of in-hospital and 30-day death. RESULTS: Seven cohort studies reporting on 9 articles with 323,788 AAA patients were included. The reported prevalence of frailty in AAA patients ranged between 2.3% and 34.6%. Pooling the results revealed that frailty was significantly associated with a higher risk of short-term all-cause mortality (adjusted risk ratios [RR] 3.20; 95% confidence intervals [CI] 1.95-5.26), long-term all-cause mortality (adjusted RR 2.86; 95% CI 2.57-3.17), and postoperative complications (adjusted RR 2.19; 95% CI 1.50-3.20) compared to non-frail individuals. However, there was no clear association between frailty and reintervention (HR 1.44; 95% CI 0.97-2.16). CONCLUSIONS: Frailty independently predicts the short and long-term survival as well as postoperative complications in patients with AAA undergoing surgery. Assessing frail status may potentially enhance surgical decision-making for these patients.

Association between glycemic variability and short-term mortality in patients with acute kidney injury: a retrospective cohort study of the MIMIC-IV database.

Acute kidney injury (AKI) represents a significant challenge to global public health problem and is associated with poor outcomes. There is still considerable debate about the effect of mean blood glucose (MBG) and coefficient of variation (CV) of blood glucose on the short-term mortality of AKI patients. This retrospective cohort study aimed to explore the association between glycemic variability and short-term mortality in patients with AKI. Data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were analyzed, including 6,777 adult AKI patients. MBG and CV on the first day of ICU admission were calculated to represent the overall glycemic status and variability during the ICU stay in AKI patients. The primary outcome indicator was ICU 30-day mortality of AKI patients. Multivariate Cox regression analysis and smoothed curve fitting were used to assess the relationship between blood glucose levels and mortality. Eventually, the ICU 30-day mortality rate of AKI patients was 23.5%. The increased MBG and CV were significantly correlated with ICU 30-day mortality (hazards ratio (HR) = 1.20, 95% confidence interval (CI) 1.14-1.27; HR = 1.08, 95% CI 1.03-1.13). The smoothed curve fitting showed a U-shaped relationship between MBG on the first day of ICU admission and ICU 30-day mortality (inflection point = 111.3 mg/dl), while CV had a linear relationship with 30-day ICU mortality. Thus, we conclude that MBG and CV were significantly associated with short-term mortality in intensive care patients with AKI. Tighter glycemic control may be an effective measure to improve the prognosis of patients with AKI.

Association Between Pretreatment Blood 25-Hydroxyvitamin D Level and Survival Outcomes in Patients With Clinically Localized Prostate Cancer: An Updated Meta-Analysis.

Studies on the prognostic value of the blood 25-hydroxyvitamin D level have yielded controversial results in prostate cancer (PCa) patients. This updated meta-analysis aimed to evaluate the association between pretreatment 25-hydroxyvitamin D level with survival outcomes among patients with clinically localized PCa. PubMed, Web of Science, and Embase databases were searched to identify studies evaluating the association of pretreatment 25-hydroxyvitamin D level with PCSM and all-cause mortality among clinically localized PCa patients. Ten cohort studies with 10,394 patients were identified. The meta-analysis revealed that PCa patients with the lowest 25-hydroxyvitamin D levels had an increased risk of PCSM (adjusted hazard ratio [HR] 1.52; 95% confidence interval [CI] 1.26-1.83; p < 0.001) and all-cause mortality (adjusted HR 1.31; 95% CI 1.00-1.90; p = 0.047) compared to those with higher reference 25-hydroxyvitamin D level. Subgroup analyses based on different sample sizes, follow-up duration, and adjusted times of blood draw also exhibited a significant association of vitamin D deficiency with the risk of PCSM. Lower pretreatment level of 25-hydroxyvitamin D may be an independent predictor of reduced survival in patients with clinically localized PCa. Measuring the pretreatment blood 25-hydroxyvitamin D level can provide valuable information for risk stratification of survival outcomes in these patients.

CircTBC1D22A inhibits the progression of colorectal cancer through autophagy regulated via miR-1825/ATG14 axis.

Distant metastasis is the main cause of death in patients with colorectal cancer (CRC). A better understanding of the mechanisms of metastasis can greatly improve the outcome of patients with CRC. Accumulating evidence suggests that circRNA plays pivotal roles in cancer progression and metastasis, especially acting as a miRNA sponge to regulate the expression of the target gene. A public database bioinformatics analysis found that miR-1825 was highly expressed in CRC tissues. In this study, miR-1825 was highly expressed in CRC tissues, which was positively correlated with lymph node metastasis and distant metastasis. In vitro and in vivo experiments confirmed that miR-1825 was positively correlated with the proliferation and migration of CRC cells. This event can be inhibited by circTBC1D22A. CircTBC1D22A can directly interact with miR-1825 and subsequently act as a miRNA sponge to regulate the expression of the target gene ATG14, which collectively advances the autophagy-mediated progression and metastasis of CRC.